Endocrine/Metabolic Agent (Enzyme)
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
One report describing the use of alglucosidase alfa in human pregnancy has been located. The animal data suggest low risk, but the dose used was very low. Untreated Pompe disease is a fatal condition with death usually related to respiratory failure (1). If a woman requires alglucosidase alfa, it should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Alglucosidase alfa, a glycoprotein produced by recombinant DNA technology, consists of the enzyme α-glucosidase (GAA) encoded by the most predominant of nine haplotypes of this gene. It is given by IV infusion every 2 weeks. Alglucosidase is indicated for patients with Pompe disease (GAA deficiency). The plasma half-life is dose-dependent ranging from 2.3 to 2.9 hours (1).
Reproduction studies have been conducted in mice. IV doses, given every other day, up to about 0.2 times the recommended bi-weekly human dose based on BSA revealed no evidence of fetal harm. A similar dose had no effect on fertility or reproductive performance in mice. Studies for carcinogenicity and mutagenicity have not been conducted (1).
It is not known if alglucosidase alfa crosses the human placenta. The molecular weight (about 99,377–109,000) and the short plasma half-life suggest that little, if any, of the glycoprotein will cross to the embryo or fetus.
A 2011 case report described the use of alglucosidase alfa (20 mg/kg every other week) throughout pregnancy in 40-year-old woman with adult-onset Pompe disease (2). Because of worsening disease, an elective cesarean section was performed at about 38 weeks’ to deliver a healthy male infant with Apgar scores of 8, 9, and 10. The infant’s weight, length, and head circumference were normal and there were no congenital anomalies. The infant was developing normally at 1 year of age (2).
BREASTFEEDING SUMMARY
One report describing the use of alglucosidase alfa during lactation has been located. In the above case report, a mother treated throughout pregnancy with the enzyme continued therapy while breastfeeding her infant (2). Before a dose, enzyme activity in her milk was 3 nmol/mL/hr, about 10% of what is measured in the milk of an unaffected mother. After infusion, the highest activity (245 nmol/mL/hr) was reached at 2.5 hours postinfusion (2). As expected, because alglucosidase alfa is a native enzyme and would be present in the infant, no adverse effects were reported in the nursing infant.
If a woman requires alglucosidase alfa for the treatment of Pompe disease, it should not be withheld because of breastfeeding.
References
1.Product information. Myozyme. Genzyme, 2007.
2.de Vries JM, Brugma JDC, Ozkan L, Steegers EAP, Reuser AJJ, van Doorn PA, van der Ploeg AT. First experience with enzyme replacement therapy during pregnancy and lactation in Pompe disease. Mol Genet Metab 2011;104:552–5.